Lumateperone Improves Acute Mania Symptoms, Trial Results Presented at Psych Congress
Key Clinical Summary
- Lumateperone 42 mg significantly improved acute manic symptoms compared with placebo in a randomized, double-blind trial of 354 adults with bipolar I disorder with or without mixed features.
- Significant improvement in Young Mania Rating Scale (YMRS) total score emerged by day 3 and was maintained through week 3.
- YMRS response rates were 45.8% with lumateperone versus 20.9% with placebo, corresponding to a number needed to treat (NNT) of 4.
Lumateperone 42 mg significantly improved symptoms of acute mania in patients with bipolar I disorder with or without mixed features compared with placebo, according to data presented in a poster at Psych Congress 2026 in New Orleans, Louisiana.
The randomized, double-blind controlled phase 3 trial enrolled 354 patients with DSM-5-TR–diagnosed bipolar I with a current episode of mania with or without mixed features. Eligible participants had a YMRS total score [TS] ≥ 20 and a Clinical Global Impression-Severity (CGI-S) score ≥ 4.
Participants were treated with either lumateperone (n = 177) or placebo (n = 177) over 3 weeks. A total of 327 patients (92.4%) completed treatment.
Study Findings
Researchers found that lumateperone significantly improved YMRS TS scores starting on day 3 and continuing through week 3 compared to placebo (LSMD, –4.8; effect size [ES], −0.69; P < .0001). Improvement in CGI-S score was also statistically significant (LSMD, –0.5; ES, −0.62; P < .0001).
The lumateperone group also demonstrated significantly greater response rates, defined as a YMRS TS reduction of at least 50% in score from baseline. Response rate was 45.8% in patients receiving lumateperone compared with 20.9% in those receiving placebo (P < .0001; number needed to treat [NNT], 4.0)
Safety and tolerability were also evaluated. Two adverse events occurred in at least 5% of lumateperone-treated patients and at least twice as frequently as with placebo: dry mouth (7.9% vs 3.4%) and nausea (7.9% vs 2.3%). Fewer than 2% of lumateperone-treated patients discontinued treatment because of adverse events.
Clinical Implications
Lumateperone is currently indicated for depressive episodes associated with bipolar I or II disorder in adults as monotherapy or adjunctive therapy, for schizophrenia, and for MDD as adjunctive therapy to antidepressants. However, this trial specifically investigated its efficacy and safety for acute mania associated with bipolar I disorder.
With treatment benefit emerging as early as day 3, the results suggest that the drug may provide a rapid onset of improvement. The investigators also reported a consistent safety and tolerability profile with low rates of discontinuation due to adverse events, supporting further evaluation of the drug for this patient population.
Reference
Cutler AJ. Lumateperone treatment of manic episodes with or without mixed features in bipolar i disorder: results from a double-blind, placebo-controlled, randomized, phase 3 trial. Poster presented at Psych Congress, 15-21, 2026; New Orleans, Louisiana.
